Objective: To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients). Methods: The family members' medical history, general physical examination and hip joint X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA were extracted from these samples. The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method. Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands. The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing. Results: The family consisted of 5 generations and 38 members. Pedigree analysis was consistent with autosomal dominant inheritance. There were 17 patients in the family, and their clinical manifestations showed abnormal walking posture in childhood, pain in hip and knee joints, and typical pathological changes of epiphyseal dysplasia on X-ray. Cartilage oligomeric matrix protein (COMP) gene c.1153G>A (p.Asp385Asn) missense heterozygous mutation was screened in proband, which was genotypically and phenotypically segregated in the pedigree. Conclusion A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family. Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.

OBJECTIVE: To explore the clinical and genetic features of a patient suspected with Juvenile Parkinson's syndrome (JP). METHODS: Clinical features of the patient were analyzed. Genomic DNA of the patient and his parents was extracted from peripheral blood samples and sequenced by exome capture sequencing. The nature and impact of detected mutations were predicted and validated. RESULTS: The patient displayed typical features including resting tremor, bradykinesia, rigidity, but with excellent response to low dose levodopa. DNA sequencing showed that she has carried compound heterozygous mutations of the Parkin gene, namely c.1381dupC and c.619-1G>C, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis predicted that both mutations are pathogenic. CONCLUSION The patient has JP caused by mutations of the Parkin gene. Exome capture sequencing is an accurate and efficient method for genetic diagnosis of such disease.
Adolescent ; Base Sequence ; Female ; Humans ; Mutation ; Parkinson Disease ; Ubiquitin-Protein Ligases ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Female ; Fetus ; Finland ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Nephrotic Syndrome ; congenital ; diagnosis ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE To detect potential mutations of the EXT1 and EXT2 genes in a pedigree affected with hereditary multiple exostosis (HME). METHODS For a four-generation family with 7 affected individuals from 17 family members,genomic DNA was extracted from peripheral venous blood samples. All exons of the EXT1 and EXT2 genes were screened for potential mutation by PCR and Sanger sequencing. RESULTS A novel heterozygous frameshift mutation c.1202delT (p.I401Tfs*2)was found in exon 4 of the EXT1 gene in the proband and the other 6 affected individuals. The same mutation was not detected among the healthy members from the family. The mutation has given rise a truncated EXT1 protein with loss of 345 amino acids. CONCLUSION A novel frameshift mutation of the EXT1 gene has been identified in a pedigree affected with HME, which has enriched the mutational spectrum of the EXT1 gene and may facilitate genetic counseling and prenatal diagnosis for the family.

OBJECTIVETo analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.

METHODSNeuropsychological profile of the child was analyzed. Color Doppler, CT and MRI were used for detecting the nodules in the body. Conventional peripheral blood karyotypes of the child and his parents were analyzed with G-banding. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities.

RESULTSThe child had mental retardation, maxillofacial dysmorphism on the right side, and irregular solid nodules on the back. The karyotypes of the child and his parents were all normal, while aCGH has identified a de novo constitutive 1.2 Mb deletion at 17q11.2 in the child. The aCGH results of his parents were normal.

CONCLUSIONThe de novo 17q11.2 microdeletion probably underlies the facial abnormalities and neurofibromatosis in the patient.

Child, Preschool ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; Comparative Genomic Hybridization ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Maxillofacial Abnormalities ; genetics ; Phenotype ; Smith-Magenis Syndrome ; genetics

Objective To evaluate the impact of particulate matter (PM) pollution on the hospitalization for respiratory diseases (RD), to estimate the avoidable economic loss by reducing the level of PM pollution, and to provide a basis for evaluating the cost-effectiveness of air pollution control. Methods The data of RD inpatients in two class-A tertiary hospitals in Wuhan from 2015 to 2019, PM concentration and meteorological data in Wuhan in the same period were collected. The generalized additive model (GAM) was used to estimate the impact of PM on the number of RD inpatients, and the cost of illness approach (COI) was used to estimate the avoidable economic loss caused by the reduction of PM concentration. Results PM pollution caused an increase in the number of RD inpatients. Each 10 g/m³ increase in PM_2.5 and PM₁₀ concentrations resulted in an increase of 1.71% and 0.71% in the number of RD inpatients, respectively. Among them, men and children aged 0-14 years were more affected. For every 10 g/m³ increase in PM_2.5 concentration, the number of hospitalized men and children aged 0-14 years increased by 1.97% and 2.65%, respectively. For every 10 g/m³ increase in PM₁₀ concentration, the number of hospitalized men and children aged 0-14 years increased by 0.87% and 0.88%, respectively. PM pollution caused 63 300 hospitalizations and 1.214 billion yuan of economic losses in 2015-2019,Wuhan. If the PM concentration is reduced to the recommended value of the World Health Organization in the same period, 194 million yuan of economic loss and 10100 hospitalizations could be avoided every year in Wuhan. Conclusion PM exposure can lead to heavy disease burden and economic loss. Taking effective measures to control PM concentration will bring great economic benefits.

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4). METHODS: Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing. RESULTS: DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic. CONCLUSION The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.
Base Sequence ; Humans ; Mutation ; Paraplegia/genetics* ; Pedigree ; Sequence Analysis, DNA ; Spastic Paraplegia, Hereditary/genetics* ; Spastin/genetics*

A female patient aged 7 years and 5 months presented with multiple skin defects of the scalp, ears, hands and in the sacrococcygeal region, and multiple joint flexion contractures of the extremities for more than 7 years. Skin examination showed skin defects of the scalp, auricles, hands and in the sacrococcygeal region, gingival swelling, and multiple joint flexion contractures of the extremities. Genetic testing of the peripheral blood revealed 2 compound heterozygous mutations c.1073delC (A359Lfs*51) and c.1073dupC (A359Cfs*13) in the anthrax toxin receptor-2 ( ANTXR2) gene in the patient, which were inherited from her mother and father respectively. The patient was diagnosed with hyaline fibromatosis syndrome. Surgical treatment was rejected, and anti-inflammatory drugs, analgesics and other drugs were administered for symptomatic treatment. During follow-up of half a year, the child occasionally had mild diarrhea, and other symptoms did not progress markedly.

Objective:To provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.

Objective: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). Methods: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. Results: The fetus was found to carry compound heterozygous variants c. 1440+ 1G>A and c. 925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. Conclusion Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.